ライフサイエンスコーパス: RNase H

1 RNase H active antisense oligonucleotides (ASOs) or smal

2 RNase H can act in a polymerization-dependent or polymer

3 RNase H can carry out primary and secondary cleavages du

4 RNase H can even effectively replace oligo(dT)-based met

5 RNase H cleavage and U1 protection assays suggest that p

6 RNase H enzymes facilitate the organisms to survive in t

7 RNase H enzymes sense the presence of ribonucleotides in

8 RNase H reduction was compounded by intrinsic RNase H de

9 RNase H-dependent PCR-enabled T-cell receptor sequencing

10 Inhibition of HIV-1 RNase H is specific, as DNA synthesis is not affected.

11 er selective inhibitors also inhibited HIV-1 RNase H with low micromolar potencies.

12 For HIV-1 RNase H, the inclusion of the cognate dNTP enhanced DNA

13 ur findings provide insights into how type 2 RNase H activity is directed during genome replication a

14 in the polymerase region of RT, and the 428, RNase H Primer Grip Adjacent, and 507 sites, located in

15 epidum and demonstrated that it is an active RNase H and adopts the RNase H fold.

16 -6, and -7 for M-MuLV significantly affected RNase H cleavage efficiency, while positions -7 and -12

17 P resistance without significantly affecting RNase H activity, whereas mutation in p51 caused NVP res

18 ucleic acids (LNAs) improve target affinity, RNase H activation and stability.

19 In general, the activity against RNase H was negligible, with only a few compounds active

20 ique clade of RecA-like ATPase domain and an RNase H-like nuclease domain tethered by a regulatory li

21 n with an HIV-1-derived vector containing an RNase H-deficient reverse transcriptase (RT).

22 he domain responsible is reported to have an RNase H-like fold.

23 These results suggest that pUL15 uses an RNase H-like, metal ion-mediated catalysis mechanism for

24 Using an RNase H negative mutant RT, we showed that a polymer tra

25 igger mRNA degradation in the nucleus via an RNase H-dependent mechanism.

26 n analysis of R-loops in vivo, we develop an RNase-H-based approach; this reveals predominant R-loop

27 proteins--beta-lactamase, interleukin-2, and RNase H--even in the absence of any ligand.

28 ) possesses both DNA polymerase activity and RNase H activity that act in concert to convert single-s

29 ed the elevated strand transfer activity and RNase H activity, in addition to the loss of azidothymid

30 tations in the connection subdomain (CN) and RNase H domain of HIV-1 reverse transcriptase (RT) were

31 show that mixing the RT polymerase, CN, and RNase H domains from different subtypes can underestimat

32 e shown that mutations in the connection and RNase H domains of HIV-1 RT may also contribute to resis

33 Sequencing of the connection and RNase H domains of the HIV-2 patients did not reveal any

34 we analyzed the polymerase, connection, and RNase H domains of RT in HIV-2 patients failing NRTI-con

35 ulation, multiple RNA biogenesis factors and RNase H act as guardians of the genome.

36 eling studies based on both the HIV-1 IN and RNase H catalytic core domains provided new structural i

37 ment of these compounds as dual HIV-1 IN and RNase H inhibitors.

38 Single nucleotide incorporation and RNase H cleavage were examined using presteady-state kin

39 Microarray mapping and RNase H cleavage identified accessible sites for oligonu

40 g short, randomized DNA oligonucleotides and RNase H cleavage.

41 requires coordination of both polymerase and RNase H activities.

42 The p66 subunit contains the polymerase and RNase H catalytic sites.

43 RT content decreased both polymerization and RNase H activity in virions.

44 cting the balance between polymerization and RNase H activity.

45 t slow PPi release allows polymerization and RNase H to occur at comparable rates.

46 , thereby attaining what has eluded RNAi and RNase H experiments: elimination of MRP RNA in the major

47 oncoding RNAs that are resistant to RNAi and RNase H-based degradation.

48 report the synthesis, thermal stability, and RNase H substrate activity of 2'-deoxy-2',4'-difluoroara

49 e to the thumb and connection subdomains and RNase H domain of the p66 subunit as well as the thumb a

50 ported that the absence of Topoisomerase and RNase H activity in Escherichia coli or Saccharomyces ce

51 , reverse transcriptase (with its associated RNase H activity), and integrase.

52 ibited reverse transcriptase (RT) associated RNase H, implying potential dual target inhibition.

53 es, consistently inhibited HIV RT-associated RNase H and polymerase with IC50s in low to submicromola

54 ues consistently inhibited HIV RT-associated RNase H in the low micromolar range in the absence of si

55 man and HIV reverse transcriptase-associated RNase H-mediated cleavage of the complement RNA strand c

56 y common substrate between the two bacterial RNase H enzymes.

57 n to access the evolutionary history between RNases H from mesophilic and thermophilic bacteria.

58 In vivo, MTOs synthesized in both RNase H-activating and steric-blocking oligonucleotide d

59 uld serve to develop dual inhibitors of both RNase H and integrase.

60 on of function between two nuclear T. brucei RNase H enzymes during RNA Pol II transcription, but ove

61 s RT pausing and RNA template degradation by RNase H activity of the RT, subsequently leading to stra

62 cesses including RNAi, target degradation by RNase H-mediated cleavage, splicing modulation, non-codi

63 oth PRI1 protein and ATP and is inhibited by RNase H treatment of the product of PRI1 synthesis.

64 e nucleotide modifications than tolerated by RNase H or RISC-dependent ASOs, with the goal of improvi

65 isense oligonucleotides (ASOs) that catalyze RNase H-mediated degradation of huntingtin mRNA, we demo

66 Overexpression of a cellular RNase H, which degrades RNA in an RNA:DNA hybrid, comple

67 ovirus and siphovirus orthologs and cellular RNase H, delineating a new evolutionary lineage among a

68 ction, which involves activation of cellular RNase H enzyme for hybridization-directed RNA cleavage.

69 One of the two cellular RNases H may assist in this process.

70 Escherichia coli RNase H is known to populate an intermediate before the

71 The folding pathway of Escherichia coli RNase H is one of the best experimentally characterized

72 oMLV) RT and also inhibited Escherichia coli RNase H.

73 not inhibit the activity of Escherichia coli RNase H.

74 are removed by two evolutionarily conserved RNase H enzymes.

75 -drug RT but higher polymerization-dependent RNase H activity.

76 It should now be possible to design RNases H that display the desired thermophilic or mesoph

77 ivo it ensures that RNase H2 is the dominant RNase H activity during nuclear replication.

78 Loss of either RNase H is lethal in mammals, whereas yeast survives the

79 Depleting endogenous RNase H activity impairs R-loop removal in Saccharomyces

80 d on these results, we propose that enhanced RNase H cleavage near the primer terminus plays a role i

81 s, a hydrolytic activity of the same enzyme (RNase H) is required to remove genomic RNA of the RNA/DN

82 ues have been tested on recombinant enzymes (RNase H and integrase) and in cell-based assays.

83 s target all HIV enzymatic activities except RNase H, which has proven to be a very difficult target

84 pendent exonuclease III, lambda exonuclease, RNase H, RNase HII, AP endonuclease, duplex-specific nuc

85 Finally, RNase H-based fragmentation analysis and 3-sequence anal

86 cleic acid conformation that is required for RNase H cleavage.

87 Mycobacterium smegmatis encodes four RNase H enzymes: RnhA, RnhB, RnhC and RnhD.

88 The addition of constraints from RNase H cleavage improves the prediction to 100% of base

89 We conclude that all three functional RNase H enzymes are present in B. subtilis NCIB 3610 and

90 The enzyme preserves the general 'RNase H-like motif' structure.

91 uplex in the vicinity of the ribonuclease H (RNase H) active site.

92 ed to allosterically inhibit ribonuclease H (RNase H) activity of human immunodeficiency virus type 1

93 rse transcriptase-associated ribonuclease H (RNase H) are both selective targets for HIV-1 chemothera

94 Ribonuclease H (RNase H) belongs to the nucleotidyl-transferase superfam

95 s polymerization-independent ribonuclease H (RNase H) cleavages of the donor template necessary for s

96 he interface between the p66 ribonuclease H (RNase H) domain and p51 thumb of human immunodeficiency

97 y HIV-1 protease cleaves the ribonuclease H (RNase H) domain of a single subunit to yield the mature

98 Two types of Ribonuclease H (RNase H) excise ribonucleotides when they form part of t

99 of ancestral proteins of the ribonuclease H (RNase H) family using ancestral sequence reconstruction

100 ranscriptase (RT) associated ribonuclease H (RNase H) for human immunodeficiency virus (HIV) drug dis

101 e well-characterized protein ribonuclease H (RNase H) from Escherichia coli populates an on-pathway i

102 ranscriptase (RT) associated ribonuclease H (RNase H) remains an unvalidated antiviral target.

103 ranscriptase (RT) associated ribonuclease H (RNase H) remains the only virally encoded enzymatic func

104 ranscriptase (RT)-associated ribonuclease H (RNase H) remains the only virally encoded enzymatic func

105 e hybrids, all organisms use ribonuclease H (RNase H) to specifically degrade the RNA portion.

106 o displayed activity against ribonuclease H (RNase H).

107 olymerase, and RT-associated ribonuclease H (RNase H).

108 Ribonucleases H (RNases H) are endonucleases which cleave the RNA moiety

109 In particular, ribonuclease HI (RNase H), an 18 kD globular protein that hydrolyzes the

110 delta), in Escherichia coli ribonuclease HI (RNase H).

111 chemotypes have been reported to inhibit HIV RNase H biochemically, few show significant antiviral ac

112 Although a number of inhibitors of HIV RNase H activity have been reported, few inhibit by dire

113 en the case for allosteric inhibition of HIV RNase H activity, providing a platform for designing imp

114 ble chemical scaffold for development of HIV RNase H inhibitors.

115 favorable binding to the active site of HIV RNase H, providing a basis for the design of more potent

116 of these analogues to the active site of HIV RNase H.

117 ajor challenge of specifically targeting HIV RNase H arises from the general lack of selectivity over

118 ossible challenges may be that targeting HIV RNase H is confronted with a steep substrate barrier.

119 simulations are reported for five homologous RNase H proteins of varying thermostabilities and enzyma

120 se activity and DNA-directed RNA hydrolysis (RNase H activity).

121 We have previously identified RNase H to be an HIV-1 protein that has the potential to

122 -activity relationship (SAR) for identifying RNase H inhibitors with antiviral activity.

123 on in p51 caused NVP resistance and impaired RNase H, demonstrating that NVP resistance may occur ind

124 C5 position that led to drastically improved RNase H inhibition and significant antiviral activity.

125 ation of the inhibitor and HIV-1 RT improves RNase H active site inhibitors and may circumvent the ob

126 explaining why R-tracts do not accumulate in RNase H-deficient cells, while double-strand breaks do.

127 ed to study the metal-ligand coordination in RNase H at different concentration of Mg(2+).

128 In conclusion, severe defects in RNase H activity alone, exemplified by the P236L mutant,

129 ance may occur independently from defects in RNase H function.

130 Moreover, in RNase H, the glutamate residue E188 has been shown to be

131 observed that the effect of the reduction in RNase H cleavage on NNRTI resistance is dependent upon t

132 y stall, so the failure of R-loop removal in RNase H-deficient bacteria becomes lethal.

133 nalysis shows that the catalytic residues in RNase H are preorganized on ps-ns time scales via a netw

134 ge assays, we show that degradation of RT in RNase H N-terminal mutants occurs in the absence of acti

135 is not required for the degradation of RT in RNase H N-terminal mutants, suggesting a role for a cell

136 e residues differs drastically from those in RNase H-like nucleases, suggesting a drifting of the act

137 immediately downstream of ES-linked VSGs in RNase H defective cells, which also have an increased am

138 the possibility of developing dual HIV-1 IN/RNase H inhibitors and obtaining new information for the

139 motherapy, and the identification of dual IN/RNase H inhibitors is an attractive strategy for new dru

140 The catalytically inactive RNase H mutation E478Q abolished this difference.

141 Indeed, RNase H-deficient cells have increased chromosomal rearr

142 ion-dependent and polymerization-independent RNase H were found to be important in creating efficient

143 pendent, but not polymerization-independent, RNase H.

144 ing modified nucleic acid residues to induce RNase H-mediated degradation of CUG-repeat transcripts.

145 ith an N-1 methyl group (9 and 10) inhibited RNase H in low micromolar range without significantly in

146 s the N-1 unsubstituted subtype 11 inhibited RNase H in submicromolar range and RT polymerase in low

147 type that potently and selectively inhibited RNase H without inhibiting HIV in cell culture.

148 primer (T/P), and consequently also inhibits RNase H activity.

149 ernalization by the cells, the intracellular RNase H acts as the "key" to specifically open the DNA/R

150 Nase H reduction was compounded by intrinsic RNase H defects in the mutant RTs.

151 ient reverse transcriptase, (ii) introducing RNase H to break up the DNA:RNA hybrid, and (iii) adding

152 8495 bound to the active site of an isolated RNase H domain of HIV-1 RT at a resolution limit of 1.71

153 The isolated RNase H domain of M-MuLV reverse transcriptase retained

154 tion and a crystal structure of the isolated RNase H domain reveals that this compound can also bind

155 s with the C-terminal domain of eRF1 via its RNase H domain to sterically occlude the binding of pept

156 endonuclease activity is inhibited by known RNase H inhibitors.

157 MMLV RT enzymes lacking RNase H activity were shown to be more sensitive to RT-q

158 ications within the oligonucleotide to limit RNase H cleavage of the non-targeted transcript.

159 ty to DNA antisense oligonucleotide-mediated RNase H digestion.

160 f protein folding and unfolding; both modern RNases H evolved to be more kinetically stable than thei

161 a C-terminal posttranslational modification, RNase H that actively hydrolyzed RNA, and exenatide that

162 Promotion of read-through by MoMLV RNase H prevents nonsense-mediated mRNA decay (NMD) of m

163 nary DRIPc-seq experiments identified mostly RNase H-resistant but exosome-sensitive RNAs that mapped

164 to the division of labor among mycobacterial RNases H by deleting the rnhA, rnhB, rnhC and rnhD genes

165 This new RNase H folds through a pathway similar to that of the p

166 K103N and Y181C mutants had normal RNase H activity; V106A, G190A, and G190S mutants had mo

167 eans for structurally guided design of novel RNase H inhibitors.

168 cular, we found that the first amino acid of RNase H never varied in over 1,850 isolates of HIV-1 tha

169 horothioate and more efficient activation of RNase H are the key advantages of mesyl phosphoramidate

170 e motion is achieved through the addition of RNase H, which selectively hydrolyses the hybridized RNA

171 CPV resolvase is dimer of RNase H superfamily domains related to Escherichia coli

172 ereby influences the catalytic efficiency of RNase H.

173 Similar results from a fragment of RNase H demonstrate that only half of the protein is sig

174 et out to trap the transient intermediate of RNase H at equilibrium by selectively destabilizing the

175 RP3-dependent responses, and introduction of RNase H, which degrades such hybrids, into infected cell

176 vels were altered by in vivo manipulation of RNase H levels did not form detectable R-loops, suggesti

177 scriptional efficiency, or overexpression of RNase H or C(1-3)A RNA can severely impair the type II t

178 have little impact on the folding pathway of RNase H.

179 probe the folding and unfolding pathways of RNase H (RNH) nascent chains stalled on the prokaryotic

180 le kinetic behavior can limit the potency of RNase H active site inhibitors.

181 ranscription is performed in the presence of RNase H, which specifically digests the RNA strands with

182 conjunction with measurements of the rate of RNase H unfolding on and off the ribosome, their results

183 uclease resistance, efficient recruitment of RNase H, and potent inhibition of key carcinogenesis pro

184 ance of the N-terminal amino acid residue of RNase H in the early life cycle of HIV-1.

185 that dictate the potency and selectivity of RNase H inhibition as well as the observed antiviral act

186 With the enhanced specificity of RNase H-dependent PCR (rhPCR), it achieves TCR-specific

187 hich was inferred from structural studies of RNase H.

188 dinium chloride (GdmCl)-induced unfolding of RNase H also begins with the formation of the DMG.

189 ficant differences between the disruption of RNase Hs and Top1 in regards to the orientation-specific

190 Based on RNase H enzymology, we enhanced single nucleotide discri

191 Zinc supported optimal RNase H activity at approximately 25 muM, similar to the

192 pocket, but it does not perturb the optimal RNase H active conformation.

193 In the absence of Top1 or RNase Hs, R-loops accumulated to substantially higher ex

194 tions by chelating divalent metal at the p66 RNase H active site.

195 Proximity of the p51 thumb to the p66 RNase H domain implied that inhibitor binding altered ac

196 chemical hurdle in the development of potent RNase H inhibitors.

197 polymerization is efficient and processive, RNase H is inefficient and periodic.

198 rnhA mutant, which is incapable of producing RNase H and thus harbors increased levels of RNA:DNA hyb

199 e were interested in one particular protein, RNase H, that is cleaved from reverse transcriptase.

200 t formation of a complex with the prototypic RNase H inhibitor beta-thujaplicinol is slow, and, once

201 ition by Prp17, Cef1 and the reoriented Prp8 RNase H-like domain.

202 ote exon ligation, bind together to the Prp8 RNase H-like domain.

203 We identified a putative RNase H from Chlorobium. tepidum and demonstrated that i

204 rted to enhance NRTI resistance, also reduce RNase H cleavage and enhance NNRTI resistance in the con

205 we hypothesized that these mutations reduce RNase H cleavage and provide more time for the NNRTI to

206 549N, Q475A, and Y501A mutants, which reduce RNase H cleavage, enhance resistance to nevirapine (NVP)

207 n on both RNA and DNA templates, and reduced RNase H cleavage.

208 erences at a cleavage site direct retroviral RNase H specificity.

209 site influence the three types of retroviral RNase H activity: internal, DNA 3'-end-directed, and RNA

210 monstrate that all three modes of retroviral RNase H cleavage share sequence determinants that may be

211 The sequence preferences of retroviral RNase H likely reflect structural features in the substr

212 assays to identify inhibitors of retroviral RNases H.

213 Ribonuclease (RNase) H enzymes that recognize and process such embedde

214 s that efficiently inhibit the ribonuclease (RNase) H activity of the human immunodeficiency virus ty

215 The ribonuclease (RNase) H class of enzymes degrades the RNA component of

216 und F3284-8495 as a specific inhibitor of RT RNase H, with low micromolar potency in vitro.

217 substrate, the C-terminal helix E of the RT RNase H domain is dynamic, characterized by severe excha

218 The methodology seizes RNase H enzyme activity to degrade the upstream and down

219 ypes carefully designed to achieve selective RNase H inhibition.

220 tary elements that rely on the PPT sequence: RNase H sequence preference and incompatibility of the p

221 s indicates that, in contrast to active site RNase H inhibitors, these thienopyrimidinones destabiliz

222 The loops are very stable and some RNase H resistant TERRA remains at the t-loop, likely ad

223 ay similar to that of the previously studied RNases H.

224 During minus-strand DNA synthesis, RNase H degrades viral RNA sequences, generating potenti

225 tive against HIV-1 replication and targeting RNase H in vitro.

226 tructure in the unfolded state of C. tepidum RNase H is more restricted than that of T. thermophilus.

227 ilus RNase H, the folding core of C. tepidum RNase H plays an important role in the unfolded state of

228 with the p51 subunit lacking the C-terminal RNase H domain.

229 esembling those of bacteriophage terminases, RNase H, integrases, DNA polymerases, and topoisomerases

230 MD calculations support the hypothesis that RNase H can accommodate three divalent metal ions in its

231 Therefore, we propose that RNase H-deficient mutants convert some R-loops into R-tr

232 Here we show that RNase H ASOs targeted to introns or exons robustly reduc

233 ribosomal force-profiling assay to show that RNase H forms a similar folding intermediate on and off

234 The RNase H active site of RT functions as a nuclease to cle

235 The RNase H activities of recombinant and virion-associated

236 The RNase H activity of reverse transcriptase carries out th

237 The RNase H activity of reverse transcriptase is required du

238 The RNase H structural fold defines a large family of nuclei

239 that it is an active RNase H and adopts the RNase H fold.

240 7u, and 8g were the most active against the RNase H activity of reverse-transcriptase, with IC50 val

241 RNA or a DNA template and did not alter the RNase H cleavage pattern.

242 Although the RNase H-dependent mechanism of inhibition of gene expres

243 cer, the reverse transcriptase (RT), and the RNase H domains.

244 rienting the RNA strand for catalysis at the RNase H active site.

245 reveals that this compound can also bind the RNase H site and retains the metal-dependent binding mod

246 ported, few inhibit by directly engaging the RNase H active site.

247 I have closely examined the RNase H domain of Prp8 in each of the structures.

248 Finally, the RNase H domain that is cleaved to generate p51 in the ma

249 of chelating two divalent metal ions in the RNase H active site.

250 ns in vif but instead a V27I mutation in the RNase H coding sequence.

251 cted by the ordering of D549 and H539 in the RNase H domain.

252 In the RNase H from Thermus thermophilus, the low DeltaC degree

253 Grip Adjacent, and 507 sites, located in the RNase H region.

254 Interestingly, the RNase H domain has different and unexpected roles in eac

255 p66 subunit and a p51 subunit that lacks the RNase H domain.

256 mical correlates of fitness by measuring the RNase H and polymerization activities of recombinant mut

257 rs closely mimic natural substrates near the RNase H domain, while their binding within the polymeras

258 pounds inhibited the polymerase, but not the RNase H function of Moloney Murine Leukemia Virus (MoMLV

259 the entire TP and RT domains and most of the RNase H domain were required for protein priming.

260 tic metals differs from other members of the RNase H family.

261 a previously uncharacterized version of the RNase H fold with multiple distinctive Zn-chelating moti

262 against IN and a moderate inhibition of the RNase H function of RT, confirming the possibility of de

263 results also indicate the importance of the RNase H N-terminal residue in the dimerization of RT sub

264 domain (amino acids 1-400, consisting of the RNase H, S1, 5'-sensor, and DNase I subdomains) of E. co

265 it is most similar to the RuvC family of the RNase H-like endonucleases.

266 Terminase nucleases resemble the RNase H-superfamily nucleotidyltransferases in folds, an

267 hese thermophilic proteins, we subjected the RNase H from Chlorobium tepidum to similar studies.

268 icinal chemistry data also revealed that the RNase H biochemical inhibition largely correlated the an

269 Additionally, we report that the RNase H complexes formed with one or both divalent ions

270 H/D exchange indicated that the RNase H domain of p66 is very flexible.

271 We found that the RNase H method performed best for chemically fragmented,

272 he bound nucleic acid prevents access to the RNase H active site, which represents a possible biochem

273 r RT, and the RNA strand moves closer to the RNase H active site.

274 yridinone-containing inhibitors bound to the RNase H active site.

275 extra structural elements in addition to the RNase H-like fold core and variations in local architect

276 ce degradation of complementary RNAs via the RNase H pathway and much is understood about that proces

277 RNA/DNA and increased interactions with the RNase H domain, including the interaction of a 2'-OH wit

278 nscriptase, which extends its Thumb with the RNase H domain.

279 ribed as well as its binding mode within the RNase H catalytic site to rationalize its selectivity.

280 sons with similar studies on T. thermophilus RNase H, identify new residues involved in this residual

281 c proteins reveals that like T. thermophilus RNase H, the folding core of C. tepidum RNase H plays an

282 Even though RNase H ASOs can reduce the level of RNA associated with

283 ASOs that function through RNase H or the RNA-induced silencing complex (RISC) resu

284 the polypurine tract (PPT), is resistant to RNase H-mediated hydrolysis and subsequently serves as a

285 igh GC skew which are partially resistant to RNase H.

286 o a sequence that was otherwise resistant to RNase H.

287 ytic domain that is topologically similar to RNase H.

288 of genuine R-loops that responded in vivo to RNase H levels and displayed classical features associat

289 protein and additional reverse transcriptase-RNase H cleavage.

290 tisense oligonucleotides (ASOs) that trigger RNase-H-mediated cleavage are commonly used to knock dow

291 critical for fine tuning catalytic turnover, RNase H processing, and drug resistance.

292 AB mutant Escherichia coli, deficient in two RNase H enzymes that remove both R-loops and incorporate

293 the riboswitch regulatory mechanism, we used RNase H cleavage assays to probe the structure of nascen

294 ranscript is cleaved within the intron using RNase H, both the 5' and 3' cleavage fragments are detec

295 an inhibitor of human immunodeficiency virus RNase H, inhibited pUL89 endonuclease activity at low-mi

296 se stability, activity in vitro and in vivo, RNase H activation and cleavage patterns (both human and

297 The mobility changes were RNase H-resistant and therefore, unlikely to have been c

298 Pre-treatment with RNase H only partially suppressed instability, supportin

299 Subsequent treatment with RNase H releases RNA-templated ligation products into so

300 e system that allows strand transfer without RNase H activity.